Elevated Galectin-3 Precedes the Development of CKD

Abstract

Galectin-3, a profibrotic mediator, is linked to the development of renal fibrosis in animal models and inversely correlates with GFR in humans, but whether galectin-3 predicts incident kidney disease is unknown. Here, we assessed renal outcomes for 2450 Framingham Offspring participants who attended examination 6 (1995–1998) and had follow-up data at examination 8 (2005–2008). Renal outcomes of interest included rapid decline in renal function (≥3 ml/min per 1.73 m² per year decline in estimated GFR [eGFR]), CKD (eGFR < 60 ml/min per 1.73 m²), and albuminuria (albumin-to-creatinine ratio ≥17 mg/g in men or ≥25 mg/g in women). We used multivariable logistic regression models to evaluate associations between galectin-3 with incident renal outcomes at examination 8. During a mean follow-up of 10.1 years, GFR declined rapidly in 241 (9.2%) participants, incident CKD developed in 277 (11.3%), and albuminuria developed in 194 (10.1%). Higher plasma levels of galectin-3 were associated with rapid decline in eGFR (per 1-SD log-galectin-3; adjusted odds ratio [OR], 1.49; 95% confidence interval [CI], 1.28 to 1.73]) and a higher risk of incident CKD (OR, 1.47; 95% CI, 1.27 to 1.71), but not with the risk of incident albuminuria. The addition of galectin-3 to clinical predictors improved the C-statistic (0.837–0.845; P=0.02) but did not reach predefined thresholds for clinically significant improvements to risk prediction based on reclassification indices. In conclusion, elevated levels of plasma galectin-3 are associated with increased risks of rapid GFR decline and of incident CKD in the community, which calls for further study in higher-risk groups.